RIP3 Cancer Research Results

RIP3, Receptor‐Interacting Protein Kinase 3: Click to Expand ⟱
Source:
Type:
RIP3 Receptor‐Interacting Protein Kinase 3
Several cancers have decreased RIP3 expression and is associated with poorer prognosis, more aggressive tumor behavior, and resistance to chemotherapies. Restoration of RIP3 may promote necroptosis, providing a potential mechanism to overcome therapy resistance.
Scientific Papers found: Click to Expand⟱
1536- Api,    Apigenin causes necroptosis by inducing ROS accumulation, mitochondrial dysfunction, and ATP depletion in malignant mesothelioma cells
- in-vitro, MM, MSTO-211H - in-vitro, MM, H2452
tumCV↓,
ROS↑, increase in intracellular reactive oxygen species (ROS)
MMP↓, caused the loss of mitochondrial membrane potential (ΔΨm)
ATP↓, ATP depletion
Apoptosis↑,
Necroptosis↑,
DNAdam↑,
TumCCA↑, delay at the G2/M phase of cell cycle
Casp3↑,
cl‑PARP↑,
MLKL↑,
p‑RIP3↑,
Bax:Bcl2↑,
eff↓, ATP supplementation restored cell viability and levels of DNA damage-, apoptosis- and necroptosis-related proteins that apigenin caused.
eff↓, N-acetylcysteine reduced ROS production and improved ΔΨm loss and cell death that were caused by apigenin.

1563- Api,  MET,    Metformin-induced ROS upregulation as amplified by apigenin causes profound anticancer activity while sparing normal cells
- in-vitro, Nor, HDFa - in-vitro, PC, AsPC-1 - in-vitro, PC, MIA PaCa-2 - in-vitro, Pca, DU145 - in-vitro, Pca, LNCaP - in-vivo, NA, NA
selectivity↑, Metformin increased cellular ROS levels in AsPC-1 pancreatic cancer cells, with minimal effect in HDF, human primary dermal fibroblasts.
selectivity↑, Metformin reduced cellular ATP levels in HDF, but not in AsPC-1 cells
selectivity↓, Metformin increased AMPK, p-AMPK (Thr172), FOXO3a, p-FOXO3a (Ser413), and MnSOD levels in HDF, but not in AsPC-1 cells
ROS↑,
eff↑, Metformin combined with apigenin increased ROS levels dramatically and decreased cell viability in various cancer cells including AsPC-1 cells, with each drug used singly having a minimal effect.
tumCV↓,
MMP↓, Metformin/apigenin combination synergistically decreased mitochondrial membrane potential in AsPC-1 cells but to a lesser extent in HDF cells
Dose∅, co-treatment with metformin (0.05, 0.5 or 5 mM) and apigenin (20 µM) dramatically increased cellular ROS levels in AsPC-1 cells
eff↓, NAC blocked the metformin/apigenin co-treatment-induced cell death in AsPC-1 cells
DNAdam↑, Combination of metformin and apigenin leads to DNA damage-induced apoptosis, autophagy and necroptosis in AsPC-1 cells but not in HDF cells
Apoptosis↑,
TumAuto↑,
Necroptosis↑,
p‑P53↑, p-p53, Bim, Bid, Bax, cleaved PARP, caspase 3, caspase 8, and caspase 9 were also significantly increased by combination of metformin and apigenin in AsPC-1
BIM↑,
BAX↑,
p‑PARP↑,
Casp3↑,
Casp8↑,
Casp9↑,
Cyt‑c↑, Cytochrome C was also released from mitochondria in AsPC-1 cell
Bcl-2↓,
AIF↑, Interestingly, autophagy-related proteins (AIF, P62 and LC3B) and necroptosis-related proteins (MLKL, p-MLKL, RIP3 and p-RIP3) were also increased by combination of metformin and apigenin
p62↑,
LC3B↑,
MLKL↑,
p‑MLKL↓,
RIP3↑,
p‑RIP3↑,
TumCG↑, in vivo
TumW↓, metformin (125 mg/kg) or apigenin (40 mg/kg) caused a reduction of tumor size compared to the control group (Fig. 7D). However, oral administration of combination of metformin and apigenin decreased tumor weight profoundly

1992- PTL,    Parthenolide induces ROS-dependent cell death in human gastric cancer cell
- in-vitro, BC, MGC803
TumCCA↑, Parthenolide induced cell cycle arrest at the G1 and S stages.
Casp↑, Parthenolide-induced caspase-dependent apoptosis and necroptosis were caused by the activation of RIP, RIP3 and MLKL
Apoptosis↑,
Necroptosis↑,
RIP1↓,
RIP3↑,
MLKL↑,
ROS↑, MGC-803 cells showed a response to ROS and oxidative stress after PN treatment.
eff↓, ROS and cytotoxicity induced by PN were significantly attenuated by a ROS scavenger catalase.

2362- SK,    RIP1 and RIP3 contribute to shikonin-induced glycolysis suppression in glioma cells via increase of intracellular hydrogen peroxide
- in-vitro, GBM, U87MG - in-vivo, GBM, NA - in-vitro, GBM, U251
RIP1↑, we found shikonin activated RIP1 and RIP3 in glioma cells in vitro and in vivo, which was accompanied with glycolysis suppression
RIP3↑,
Glycolysis↓,
G6PD↓, shikonin-induced decreases of glucose-6-phosphate and pyruvate and downregulation of HK II and PKM2
HK2↓,
PKM2↓,
H2O2↑, shikonin also triggered accumulation of intracellular H2O2 and depletion of GSH and cysteine
GSH↓,
ROS↑, It was documented that inhibition of HK II with its inhibitor 3-bromopyruvate or knockdown of its level resulted in accumulation of ROS

2197- SK,    Shikonin derivatives for cancer prevention and therapy
- Review, Var, NA
ROS↑, This compound accumulates in the mitochondria, which leads to the generation of reactive oxygen species (ROS), and deregulates intracellular Ca2+ levels.
Ca+2↑,
BAX↑, shikonin alone by increasing the expression of the pro-apoptotic Bax protein and decreasing the expression of the anti-apoptotic Bcl2 protein
Bcl-2↓,
MMP9↓, This treatment also inhibited metastasis by decreasing the expression of MMP-9 and NF-kB p65 without affecting MMP-2 expression.
NF-kB↓,
PKM2↓, Figure 4
Hif1a↓,
NRF2↓,
P53↑,
DNMT1↓,
MDR1↓,
COX2↓,
VEGF↓,
EMT↓,
MMP7↓,
MMP13↓,
uPA↓,
RIP1↑,
RIP3↑,
Casp3↑,
Casp7↑,
Casp9↑,
P21↓,
DFF45↓,
TRAIL↑,
PTEN↑,
mTOR↓,
AR↓,
FAK↓,
Src↓,
Myc↓,
RadioS↑, shikonin acted as a radiosensitizer because of the high ROS production it induced.

2188- SK,    Molecular mechanism of shikonin inhibiting tumor growth and potential application in cancer treatment
- Review, Var, NA
ROS↑, their induction of reactive oxygen species production, inhibition of EGFR and PI3K/AKT signaling pathway activation, inhibition of angiogenesis and induction of apoptosis and necroptosis
EGFR↓,
PI3K↓,
Akt↓,
angioG↓,
Apoptosis↑,
Necroptosis↑,
GSH↓, leading to the increased consumption of reduced glutathione (GSH) and increased Ca2+ concentration in the cells and destroying the mitochondrial membrane potential.
Ca+2↓,
MMP↓,
ERK↓, 24 h of treatment with shikonin, ERK 1/2 and AKT activities were significantly inhibited, and p38 activity was upregulated, which ultimately led to pro-caspase-3 cleavage and triggered the apoptosis of GC cells.
p38↑,
proCasp3↑,
eff↓, pretreated with the ROS scavengers NAC and GSH before treatment with shikonin, the production of ROS was significantly inhibited, the cytotoxicity of shikonin was attenuated
VEGF↓, shikonin can inhibit the expression of VEGF
FOXO3↑, Activated FOXO3a/EGR1/SIRT1 signaling
EGR1↑,
SIRT1↑,
RIP1↑, Upregulation of RIP1 and RIP3
RIP3↑,
BioAv↓, limitations caused by its poor water solubility, it has a short half-life and nonselective biological distribution
NF-kB↓, Shikonin can also prevent the activation of NF-κB by AKT and then downregulate the expression of Bcl-xl,
Half-Life↓, due to the limitations caused by its poor water solubility, it has a short half-life and nonselective biological distribution.

2222- SK,    The anti-tumor effect of shikonin on osteosarcoma by inducing RIP1 and RIP3 dependent necroptosis
- in-vitro, OS, U2OS - in-vitro, OS, 143B - in-vivo, NA, NA
Necroptosis↑, Shikonin induced necroptosis in osteosarcoma cells
RIP1↑, Shikonin induced necroptosis via upregulating RIP1 and RIP3
RIP3↑,
OS↑, Shikonin prolonged the survival of metastatic disease
P53↑, protein level of p53 was increased after treated with shikonin for 8 hours

1342- SK,    RIP1 and RIP3 contribute to shikonin-induced DNA double-strand breaks in glioma cells via increase of intracellular reactive oxygen species
- in-vitro, GBM, NA - in-vivo, NA, NA
RIP1↑,
RIP3↑,
DNAdam↑, DNA DSBs in vitro and in vivo
ROS↑,
GSH↓, depletion of GSH


Showing Research Papers: 1 to 8 of 8

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 8

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

GSH↓, 3,   H2O2↑, 1,   NRF2↓, 1,   ROS↑, 7,  

Mitochondria & Bioenergetics ⓘ

AIF↑, 1,   ATP↓, 1,   MMP↓, 3,  

Core Metabolism/Glycolysis ⓘ

G6PD↓, 1,   Glycolysis↓, 1,   HK2↓, 1,   PKM2↓, 2,   SIRT1↑, 1,  

Cell Death ⓘ

Akt↓, 1,   Apoptosis↑, 4,   BAX↑, 2,   Bax:Bcl2↑, 1,   Bcl-2↓, 2,   BIM↑, 1,   Casp↑, 1,   Casp3↑, 3,   proCasp3↑, 1,   Casp7↑, 1,   Casp8↑, 1,   Casp9↑, 2,   Cyt‑c↑, 1,   MLKL↑, 3,   p‑MLKL↓, 1,   Myc↓, 1,   Necroptosis↑, 5,   p38↑, 1,   RIP1↓, 1,   RIP1↑, 5,   TRAIL↑, 1,  

Transcription & Epigenetics ⓘ

tumCV↓, 2,  

Autophagy & Lysosomes ⓘ

LC3B↑, 1,   p62↑, 1,   TumAuto↑, 1,  

DNA Damage & Repair ⓘ

DFF45↓, 1,   DNAdam↑, 3,   DNMT1↓, 1,   P53↑, 2,   p‑P53↑, 1,   p‑PARP↑, 1,   cl‑PARP↑, 1,  

Cell Cycle & Senescence ⓘ

P21↓, 1,   TumCCA↑, 2,  

Proliferation, Differentiation & Cell State ⓘ

EMT↓, 1,   ERK↓, 1,   FOXO3↑, 1,   mTOR↓, 1,   PI3K↓, 1,   PTEN↑, 1,   Src↓, 1,   TumCG↑, 1,  

Migration ⓘ

Ca+2↓, 1,   Ca+2↑, 1,   FAK↓, 1,   MMP13↓, 1,   MMP7↓, 1,   MMP9↓, 1,   RIP3↑, 7,   p‑RIP3↑, 2,   uPA↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   EGFR↓, 1,   EGR1↑, 1,   Hif1a↓, 1,   VEGF↓, 2,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   NF-kB↓, 2,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   Dose∅, 1,   eff↓, 5,   eff↑, 1,   Half-Life↓, 1,   MDR1↓, 1,   RadioS↑, 1,   selectivity↓, 1,   selectivity↑, 2,  

Clinical Biomarkers ⓘ

AR↓, 1,   EGFR↓, 1,   Myc↓, 1,  

Functional Outcomes ⓘ

OS↑, 1,   TumW↓, 1,  
Total Targets: 85

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: RIP3, Receptor‐Interacting Protein Kinase 3
5 Shikonin
2 Apigenin (mainly Parsley)
1 Metformin
1 Parthenolide
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:%  Target#:1066  State#:%  Dir#:2
  wNotes=on  sortOrder:rid,rpid

 

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